Dynamic Changes in Collagen Organization Modulate Cervical Remodeling During Pregnancy and Parturtion: New Insights and the Potential for Improved Clinical Tools to Combat Preterm Birth

Preterm birth affects approximately 500,000 infants in the Unites States alone and is the second highest cause of infant morbidity in this country. Obstetricians still do not have reliable tools to diagnose or treat women presenting with premature labor. Understanding mechanisms by which the cervix remodels during term and preterm pregnancy is critical to formulate better methods for detection and treatment of preterm birth. The focus of this study was to identify how cervical collagen is reorganized throughout pregnancy to allow the cervix to become compliant for parturition. Beginning early in pregnancy a reduction in cervical collagen cross-links as well as a decline in matricellular proteins contribute to the changing cervical extracellular matrix environment. These cumulative changes result in increased collagen fibril diameter, as well as a progressive increase in tissue distensibility and a decline in tissue stiffness. Changes in collagen morphology over pregnancy can be visualized via non-invasive second harmonic generation (SHG). Quantification of specific morphological features such as collagen fiber diameter or porosity reveal progressive changes that allow one to distinguish stages in pregnancy. In addition, analysis of SHG images from two preterm birth models as well as one postterm pregnancy model validate the ability to use quantitative morphological measurements to distinguish normal from abnormal cervical remodeling. These findings suggest SHG technology is a powerful tool that may have potential clinically to predict preterm birth. In closing these studies have identified early and progressive changes in processing and assembly of collagen fibrils as well as changes in other ECM components that likely contribute to the incremental change in cervical tensile strength required for birth.